Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans.
Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans.
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胆固醇侧链裂解酶基因（CYP11A）的复合杂合突变导致人类先天性肾上腺皮质功能不全。
DOI：
10.1210/jcem.87.8.8763
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Toshiaki Tanaka
中科院分区：
文献类型：
--
作者：
N. Katsumata;Masatoshi Ohtake;T. Hojo;E. Ogawa;T. Hara;N. Sato;Toshiaki Tanaka
胆固醇侧链裂解酶(P450scc)催化线粒体中胆固醇转化为孕烯醇酮，是所有类固醇激素生物合成的第一步。到目前为止，还没有在人类中描述CYP11A的纯合子或复合杂合突变。在这里，我们描述了一例父母健康的先天性肾上腺皮质功能不全患者的细胞色素P11A基因的新型复合杂合子突变。一个突变是母系遗传的R353W突变，通过单一氨基酸替换导致P450scc活性显著降低，表明Arg(353)是P450scc活性的关键氨基酸残基。另一个突变是父本等位基因中的从头A189V突变，该突变不会通过单一氨基酸替换影响P450scc的活性，而是一个剪接突变，从而产生了一个新的选择性剪接供体位点。它导致开放阅读框中61个核苷酸的缺失，从而部分失活了CYP11A。这些实验数据与临床结果一致，表明患者部分保留了合成肾上腺类固醇激素的能力。这是首次报道先天性肾上腺皮质功能不全的CYP11A突变的复合杂合子和表型正常的杂合子。
Cholesterol side-chain cleavage enzyme (P450scc) catalyzes the conversion of cholesterol to pregnenolone in mitochondria, which is the first step in the biosynthesis of all steroid hormones. Until now, no homozygous or compound heterozygous mutations in CYP11A have been described in humans. Here we describe novel compound heterozygous mutations in CYP11A in a patient with congenital adrenal insufficiency born to healthy parents. One mutation, a maternally inherited R353W mutation, resulted in markedly reduced P450scc activity by the single amino acid substitution, indicating that Arg(353) is a crucial amino acid residue for P450scc activity. The other mutation, a de novo A189V mutation in the paternal allele, did not affect the P450scc activity by the single amino acid substitution and turned out to be a splicing mutation, which created a novel alternative splice-donor site. It resulted in a deletion of 61 nucleotides in the open reading frame and thus partially inactivated CYP11A. These experimental data are consistent with the clinical findings indicating that the patient had partially preserved ability to synthesize adrenal steroid hormones. This is the first report of the compound heterozygote for the CYP11A mutations with congenital adrenal insufficiency and the phenotypically normal heterozygote in humans.
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大鼠卵巢颗粒细胞和黄体中胆固醇侧链裂解细胞色素 P-450 (P-450scc) 的环 AMP 依赖性和非依赖性调节。
DOI：
--
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Oonk,RB;Krasnow,JS;Beattie,WG;Richards,JS
通讯作者：
Richards,JS
影响因子：
158.5
作者：
Bose, HS;Sugawara, T;Miller, WL
通讯作者：
Miller, WL
兔子遗传性先天性肾上腺增生症是由编码细胞色素 P450 胆固醇侧链裂解酶的基因缺失引起的。
影响因子：
4.8
作者：
Yang,X;Iwamoto,K;Wang,M;Artwohl,J;Mason,JI;Pang,S
通讯作者：
Pang,S
影响因子：
20.3
作者：
D. Stocco;B. Clark
通讯作者：
D. Stocco;B. Clark
影响因子：
56.9
作者：
LIN, D;SUGAWARA, T;MILLER, WL
通讯作者：
MILLER, WL